HER3
HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.
HER3 has weak kinase activity but is the preferred dimerisation partner of HER2 and a major driver of resistance to EGFR and HER2 inhibitors. Patritumab deruxtecan (HER3-DXd) and the EGFR×HER3 bispecific ADC izalontamab brengitecan make it a delivery target rather than a signalling target.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.
- 1 · What it is
HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.
- 2 · What goes wrong in cancer
Neuregulin (NRG1) ligand; NRG1 fusions are rare drivers targeted by zenocutuzumab. Broadly expressed across breast, lung, and colorectal cancers.
- 3 · How drugs use it
4 products aim at HER3: antibodies, antibody-drug conjugates and bispecific antibodies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Biology
Neuregulin (NRG1) ligand; NRG1 fusions are rare drivers targeted by zenocutuzumab. Broadly expressed across breast, lung, and colorectal cancers.
- Breast cancer (all subtypes)
- EGFR-mutant NSCLC
- Colorectal
- NRG1-fusion tumours
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 80-90% | IHC, any expression | EGFR-mutant NSCLC in HERTHENA-Lung01 | Wikipedia |
| Triple-negative breast cancer | 50-70% | IHC, any expression | Wikipedia | |
| HR-positive / HER2-negative breast cancer | 50-70% | IHC, any expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Izalontamab brengitecan is the first bispecific ADC to succeed in a phase 3 trial, hitting two growth receptors at once in triple-negative breast cancer.
A HER3-directed ADC with Enhertu's payload, active in lung and all subtypes of breast cancer, but with a bumpy regulatory road.
A second HER2 antibody that binds a different spot from trastuzumab, blocking HER2 from pairing with HER3; together they extended survival by 16 months in CLEOPATRA.
Zenocutuzumab is the first drug for cancers driven by NRG1 gene fusions, working by blocking HER3 from receiving its growth signal.
Latest papers
topQuery for this target: (TITLE:"HER3" OR ABSTRACT:"HER3" OR TITLE:"ERBB3" OR ABSTRACT:"ERBB3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HER3, not a curated reading list.